The present invention relates in general to surface-located proteins from gram-positive bacteria, and in particular to a group of proteins that contain highly conserved sequence motifs. In addition, the invention relates to polyclonal and monoclonal antibodies which can recognize these proteins and which can recognize the conserved motifs. Further, the invention relates to the use of the proteins, conserved motifs and antibodies generated thereto in compositions and methods used to treat or prevent infections and other pathogenic conditions caused by a wide-array of gram-positive bacteria.
Bacterial surface proteins of gram-positive bacteria are known to be important during the infection process since they mediate bacterial attachment to host tissues, and/or interact with the host immune system. For example, in the gram-positive bacteria Staphylococcus aureus, several of these proteins have been well characterized and were found to bind extracellular matrix proteins such as collagen, fibronectin, fibrinogen, as well as immunoglobulin G. These binding proteins include fibronectin binding proteins such as disclosed in U.S. Pat. Nos. 5,175,096; 5,320,951; 5,416,021; 5,440,014; 5,571,514; 5,652,217; 5,707,702; 5,789,549; 5,840,846; 5,980,908; and 6,086,895; fibrinogen binding proteins such as disclosed in U.S. Pat. Nos. 6,008,341 and 6,177,084; and collagen binding proteins as disclosed in 5,851,794 and 6,288,214; all of these patents incorporated herein by reference.
Previous studies have shown that the collagen and fibronectin binding proteins have been shown to contribute to the virulence of S. aureus in animal models. In addition, immunization of mice with certain of these binding protein has been shown in some cases to provide protection from septic death due to S. aureus. However, in some cases, certain formulations based on bacterial proteins from specific gram-positive bacteria such as S. aureus were not always effective in treating patients, and moreover these formulations will generally be species specific and thus do not generally afford protection against infection from a variety of gram-positive bacteria. Accordingly, it is very important to develop ways of locating surface proteins which will be utilized effectively in methods of treating or preventing infection, and in particular it is highly desirable to develop methods of treatment which can be utilized in a broad-based application to treat or prevent a wide variety of infections caused by gram-positive bacteria.
Accordingly, it is an object of the present invention to provide methods for isolating proteins from gram-positive bacteria which can be utilized in methods of treating or preventing a wide range of infections caused by gram-positive bacteria.
It is another object of the present invention to provide surface proteins from gram-positive bacteria that have highly conserved sequence motifs near their carboxyl termini which can be utilized to generate antibodies that will be protective against a wide variety of gram positive bacteria.
It is further an object of the present invention to provide a method of generating an immune response to a wide variety of gram-positive bacteria by administering an immunogenic amount of an isolated peptide sequence which is highly conserved in gram positive bacteria or by administering proteins which include these highly conserved sequence motifs.
It is a further object of the present invention to provide a vaccine for treating or preventing infection from gram-positive bacteria which comprises an isolated peptide sequence which is highly conserved in gram positive bacteria or a protein which includes one or more of these highly conserved sequence motifs in an amount effective to generate an immune response to said peptides or proteins.
It is still further an object to provide compositions for treating or preventing an infection from gram-positive bacteria which comprise an isolated peptide sequence which is highly conserved in gram positive bacteria or a protein which includes one or more of these highly conserved sequence motifs and a pharmaceutically acceptable vehicle, carrier or excipient.
It is still further an object of the present invention to provide isolated antibodies which recognize these highly conserved sequence motifs or proteins which contain said motifs, and to utilize these antibodies in treating or preventing infection caused by a broad range of gram-positive bacteria.
It is an additional object of the present invention to provide diagnostic kits which can utilize the conserved sequences, proteins, and/or antibodies in accordance with the invention in order to diagnose and identify infections caused by gram-positive bacteria.
These and other objects are provided by virtue of the present invention which comprises the identification, isolation, and/or purification of highly conserved amino acid sequences from gram positive bacteria and proteins which contain said sequences, and the use of these sequences and/or proteins to treat or prevent infections caused by a wide range of gram-positive bacteria. In addition, the invention comprises monoclonal and polyclonal antibodies which recognize these sequences and proteins, as well as vaccines and other pharmaceutical compositions which utilize these peptide sequences and proteins, and methods of eliciting an immune response against a broad range of gram positive bacteria by administering the peptides and/or proteins to a human or animal in an amount effective to generate an immune response. The sequences and proteins of the present invention can thus be used in methods or achieving passive or active immunity in patients so as to treat or prevent a wide range of infections caused by gram-positive bacteria.
These embodiments and other alternatives and modifications within the spirit and scope of the disclosed invention are described in, or will become readily apparent from, reference to the detailed description of the preferred embodiments provided herein below.